Regulatory role of miRNAs on Wnt/ß-catenin signaling in tumorigenesis of glioblastoma.

Glioblastoma (GBM) is one of the most aggressive tumors in the brain with high mortality worldwide. Despite recent advances in therapeutic strategies, the survival rate remains low in patients with GBM. The pathogenesis of GBM is a very complicated process involving various genetic mutations affecting several oncogenic signaling pathways like Wnt/ß-catenin axis. Overactivation of the Wnt/ß-catenin signaling pathway is associated with decreased survival and poor prognosis in patients with GBM. MicroRNAs (miRNAs) were shown to play important roles in the regulation of cell proliferation, differentiation, apoptosis, and tumorigenesis by modulating the expression of their target genes. Aberrant expression of miRNAs were reported in various human malignancies including GBM, breast, colorectal, liver, and prostate cancers, but little is known about their cellular mechanisms. Therefore, recognition of the expression profile and regulatory effects of miRNAs on the Wnt/ß-catenin pathway may offer a novel approach for the classification, diagnosis, prognosis, and treatment of patients with GBM. This review summarizes previous data on the modulatory role of miRNAs on the Wnt/ß-catenin pathway implicated in tumorigenesis of GBM.

The applications of epigallocatechin gallate (EGCG)-nanogold conjugate in cancer therapy.

Cancer has recently increased the death toll worldwide owing to inadequate therapy and decreased drug bioavailability. Long-term and untargeted chemotherapeutic exposure causes toxicity to healthy cells and drug resistance. These challenges necessitate the development of new methods to increase drug efficacy. Nanotechnology is an emerging field in the engineering of new drug delivery platforms. The phytochemical epigallocatechin gallate (EGCG), the main component of green tea extract and its most bioactive component, offers novel approaches to cancer cell eradication. The current review focuses on the nanogold-based carriers containing EGCG, with an emphasis on the chemotherapeutic effects of EGCG in cancer treatment. The nanoscale vehicle may improve the EGCG solubility and bioavailability while overcoming constraints and cellular barriers. This article reviewed the phytochemical EGCG-based gold nanoplatforms and their major anticancer applications, both individually, and in combination therapy in a few cases.

The role of heat shock proteins in metastatic colorectal cancer: A review.

Heat shock proteins (HSPs) are a large molecular chaperone family classified by their molecular weights, including HSP27, HSP40, HSP60, HSP70, HSP90, and HSP110. HSPs are likely to have antiapoptotic properties and participate actively in various processes such as tumor cell proliferation, invasion, metastases, and death. In this review, we discuss comprehensively the functions of HSPs associated with the progression of colorectal cancer (CRC) and metastasis and resistance to cancer therapy. Taken together, HSPs have numerous clinical applications as biomarkers for cancer diagnosis and prognosis and potential therapeutic targets for CRC and its related metastases.

Glioblastoma, an opportunity T cell trafficking could bring for the treatment.

PURPOSE: Infiltrating into the vital structure of the brain, located in the inaccessible anatomical region, and having molecular heterogeneity, glioblastoma (GBM) -with no doubt- is one of the deadliest cancers. Using the blood and brain barrier (BBB), GBM makes a shield to restrict the reach of chemotherapeutic agents to the tumor site and evolves a unique microenvironment to furnish all the essentials for cancer cells survival to conceal neoplastic cells from immunosurveillance. METHODS: 99 papers which met the criteria of eligibility were included in this review by consensus. The included articles were classified based on their design and level of evidence. RESULTS: Given this characteristic, immunotherapies for a while enjoyed unprecedented attention as a solution for GBM treatment; however, it did not take long before the enthusiasm for their application was muted. It became apparent that cancer cells intelligently find a way to manipulate the anti-tumor responses of agents by attracting immunosuppressive lymphocytes into the brain using the lymphatic vessels. This event makes GBM a good model for immunotherapy resistance. However, the presence of lymphatic vessels has fired up an idea of the adoptive attraction of effector T lymphocytes to the tumor milieu. This was when engineering and cloning technologies, which have given life to one of the recent treatment strategies using artificial T cells named chimeric antigen receptors (CAR) T-cells, came to action to design specific CAR T-cells for the treatment of GBM. CONCLUSION: The present review summarizes the recent advances in CAR T-cell-based treatments in GBM and discusses why this approach could be positioned as a pillar of the next-generation of immunotherapies for this type of brain tumor.

The Role of Micro RNAs in Regulating PI3K/AKT Signaling Pathways in Glioblastoma.

Glioblastoma is a type of brain cancer with aggressive and invasive nature. Such features result from increased proliferation and migration and also poor apoptosis of glioma cells leading to resistance to current treatments such as chemotherapy and radiotherapy. In recent studies, micro RNAs have been introduced as a novel target for treating glioblastoma via regulation of apoptotic signaling pathway, remarkably PI3K/AKT, which affect cellular functions and blockage or progression of the tumor. In this review, we focus on PI3K/AKT signaling pathway and other related apoptotic processes contributing to glioblastoma and investigate the role of micro RNAs interfering in apoptosis, invasion and proliferation of glioma through such apoptotic processes pathways. Databases NCBI, PubMed, and Web of Science were searched for published English articles using keywords such as 'miRNA OR microRNA', 'Glioblastoma', 'apoptotic pathways', 'PI3K and AKT', 'Caspase signaling Pathway' and 'Notch pathway'. Most articles were published from 7 May 2015 to 16 June 2020. This study focused on PI3K/AKT signaling pathway affecting glioma cells in separated subparts. Also, other related apoptotic pathways as the Caspase cycle and Notch have been also investigated. Nearly 40 miRNAs were found as tumor suppressors or onco-miRNA, and their targets, which regulated subcomponents participating in proliferation, invasion, and apoptosis of the tumoral cells. Our review reveals that miRNAs affect key molecules in signaling apoptotic pathways, partly PI3K/AKT, making them potential therapeutic targets to overcome the tumor. However, their utility as a novel treatment for glioblastoma requires further examination and investigation.

Role of regulatory miRNAs of the Wnt/ ß-catenin signaling pathway in tumorigenesis of breast cancer.

Breast cancer is the most commonly diagnosed malignancy in women worldwide. Recently, uncontrolled expression of microRNAs was detected in several human disorders like cardiovascular, neurological, intestinal and autoimmunity diseases. MicroRNAs (miRNAs) are now investigated as novel prognostic and diagnostic biomarkers for several solid tumors like breast, lung, and gastrointestinal cancers. Current data suggest that miRNAs are implicated in various oncogenic processes implicated in breast cancer carcinogenesis trough modulating canonical Wnt pathway. Aberrant activation of Wnt/b-catenin signaling was shown to be significantly associated with tumor progression and poor prognosis in patients with breast cancer. This review presents recent findings on the molecular mechanism of microRNAs in regulation of Wnt/ß-catenin signaling involved in tumorigenesis of breast cancer.